scholarly journals The PICO Study: Impact of Phenylalanine on Cognitive, Cerebral and Neurometabolic Parameters in Adult Patients with Phenylketonuria – a Randomized, Placebo-Controlled, Crossover, Non-inferiority Trial

2019 ◽  
Author(s):  
Roman Trepp ◽  
Raphaela Muri ◽  
Lenka Bosanska ◽  
Stephanie Abgottspon ◽  
Michel Hochuli ◽  
...  
Keyword(s):  
Working Memory ◽  
Memory Task ◽  
Brain Regions ◽  
Primary Objective ◽  
Adult Patients ◽  
Target Range ◽  
Neural Activation ◽  
Level Of Evidence ◽  
Double Blind ◽  
The Brain

Abstract Background The population of adult patients with early-treated phenylketonuria (PKU) following newborn screening is growing substantially. The ideal target range of blood Phe levels in adults outside pregnancy is discussed controversially. Therefore, prospective intervention studies are needed to evaluate the effects of an elevated Phe concentration on cognition and structural, functional and neurometabolic parameters of the brain. Methods The PICO (Phenylalanine and Its Impact on Cognition) Study evaluates the effect of a 4-week phenylalanine (Phe) load on cognition and cerebral parameters in 30 adults with early-treated PKU in a double-blind, randomized, placebo-controlled, crossover, non-inferiority trial. The primary objective of the PICO Study is to prospectively assess whether a temporarily elevated Phe level influences cognitive performance in adults with early-treated PKU. As secondary objective, the PICO Study will elucidate cerebral and neurometabolic mechanisms, which accompany changes in Phe concentration using advanced neuroimaging methods. In addition to the intervention study, cognition, structural and functional parameters of the brain of adult patients with early-treated PKU will be cross-sectionally compared to healthy controls, who will be comparable with regard to age, gender and education level. Advanced MR-techniques will be used to investigate intensity of neural activation during the working memory task (fMRI), strength of functional connectivity between brain regions related to performance in working memory (rsfMRI), white matter integrity (DTI), cerebral blood flow (ASL) and brain Phe concentrations (MRS). Discussion Using a combination of neuropsychological and neuroimaging data, the PICO study will considerably contribute to improve the currently insufficient level of evidence on how adult patients with early-treated PKU should be managed.

scholarly journals The PICO Study: Impact of Phenylalanine on Cognitive, Cerebral and Neurometabolic Parameters in Adult Patients with Phenylketonuria: a Randomized, Placebo-Controlled, Crossover, Non-inferiority Trial

2019 ◽  
Author(s):  
Roman Trepp ◽  
Raphaela Muri ◽  
Stephanie Abgottspon ◽  
Lenka Bosanska ◽  
Michel Hochuli ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Adult Patients ◽  
University Hospital ◽  
Target Range ◽  
Neural Activation ◽  
Healthy Controls ◽  
Double Blind ◽  
The University ◽  
The Brain ◽  
Back Task

Abstract Background The population of adult patients with early-treated phenylketonuria (PKU) following newborn screening is growing substantially. The ideal target range of blood Phenylalanine (Phe) levels in adults outside pregnancy is a matter of debate. Therefore, prospective intervention studies are needed to evaluate the effects of an elevated Phe concentration on cognition and structural, functional and neurometabolic parameters of the brain. Methods The PICO (Phenylalanine and Its Impact on Cognition) Study evaluates the effect of a 4-week Phe load on cognition and cerebral parameters in adults with early-treated PKU in a double-blind, randomized, placebo-controlled, crossover, non-inferiority trial. Participants: 30 adult patients with early-treated PKU and 30 healthy controls comparable to patients with regard to age, sex and educational level will be recruited from the University Hospitals Bern and Zurich, Switzerland. Patients are eligible for the study if they are age ≥18 years and have PKU diagnosed after a positive newborn screening and treated with a Phe-restricted diet starting within the first 30 days of life. Intervention: The cross-over intervention consists of a 4-week oral Phe or placebo administration in patients with PKU. The study design mimics a Phe-restricted and a Phe-unrestricted diet using a double-blinded, placebo-controlled approach. Objectives: The primary objective of the PICO Study is to prospectively assess whether a temporarily elevated Phe-level influences cognitive performance (working memory assessed with a n-back task) in adults with early-treated PKU. As secondary objective, the PICO Study will elucidate cerebral (fMRI: neural activation during a n-back task; rsfMRI: functional connectivity at rest; DTI: white matter integrity; ASL: cerebral blood flow) and neurometabolic mechanisms (cerebral Phe-level), which accompany changes in Phe concentration. Cognition, structural and functional parameters of the brain of adult patients with early-treated PKU will be cross-sectionally compared to healthy controls. All assessments will take place at the University Hospital Bern, Switzerland. Randomization: Central randomization will be used to assign participants to the different treatment arms with age, sex and center serving as stratification factors. Randomization lists will be generated by an independent statistician. Blinding: All trial personnel but the statistician generating the randomization list and the personnel at the facility preparing the interventional product are blinded to the assigned treatment.

scholarly journals Working memory task induced neural activation: a simultaneous PET/fMRI study

NeuroImage ◽  
2021 ◽  
pp. 118131
Author(s):  
Isabelle KD Ripp ◽  
Lara A Wallenwein ◽  
Qiong Wu ◽  
Monica Emch ◽  
Kathrin Koch ◽  
...  
Keyword(s):  
Working Memory ◽  
Memory Task ◽  
Neural Activation ◽  
Fmri Study

scholarly journals Acute Intake of a Grape and Blueberry Polyphenol-Rich Extract Ameliorates Cognitive Performance in Healthy Young Adults During a Sustained Cognitive Effort

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 650 ◽  
Author(s):  
Pierre Philip ◽  
Patricia Sagaspe ◽  
Jacques Taillard ◽  
Claire Mandon ◽  
Joël Constans ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Performance ◽  
Visual Information ◽  
Fold Increase ◽  
Cognitive Effort ◽  
Double Blind Study ◽  
Level Of Evidence ◽  
Double Blind ◽  
Safe Alternative ◽  
Memory And Attention

Despite an increasing level of evidence supporting the individual beneficial effect of polyphenols on cognitive performance, information related to the potential synergistic action of these phytonutrients on cognitive performance during a prolonged cognitive effort is currently lacking. This study investigated the acute and sustained action of a polyphenols-rich extract from grape and blueberry (PEGB), on working memory and attention in healthy students during a prolonged and intensive cognitive effort. In this randomised, cross-over, double blind study, 30 healthy students consumed 600 mg of PEGB or a placebo. Ninety minutes after product intake, cognitive functions were assessed for one hour using a cognitive demand battery including serial subtraction tasks, a rapid visual information processing (RVIP) task and a visual analogical scale. Flow-mediated dilation (FMD) and plasma flavan-3-ols metabolites quantification were also performed. A 2.5-fold increase in serial three subtraction variation net scores was observed following PEGB consumption versus placebo (p < 0.001). A trend towards significance was also observed with RVIP percentage of correct answers (p = 0.058). No treatment effect was observed on FMD. Our findings suggest that consumption of PEGB coupled with a healthy lifestyle may be a safe alternative to acutely improve working memory and attention during a sustained cognitive effort.

Distinct Effects of D9-tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
P. Fusar-Poli
Keyword(s):  
Emotional Processing ◽  
Electrodermal Activity ◽  
Brain Regions ◽  
Posterior Cingulate Cortex ◽  
Psychotic Symptoms ◽  
Neural Activation ◽  
Double Blind ◽  
Posterior Cingulate ◽  
Fearful Faces ◽  
Scanning Session

Aims:Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown.Method:Fifteen healthy English-native right-handed men were studied on three separate occasions using an event-related fMRI paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10mg of D-9-THC, 600mg of CBD, or a placebo, in a double-blind, randomised, placebo controlled design. Electrodermal activity (Skin Conductance Response, SCR) and objective and subjective ratings of anxiety were recorded durign the scanning.Results:D-9THC increased anxiety, as well as levels of intoxication, sedation and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of D-9THC but decreased following administration of CBD. CBD attenuated the BOLD signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and posterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. D-9-THC mainly modulated activation in frontal and parietal areas.Conclusions:D-9-THC and CBD had clearly distinct effects on the neural, eclectrodermal and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of D-9-THC may be related to effects in other brain regions.

Executive Functions in Adolescents with Autism Spectrum Disorder

2017 ◽  
pp. 67-90
Author(s):  
Yael Dai ◽  
Inge-Marie Eigsti
Keyword(s):  
Autism Spectrum Disorder ◽  
Working Memory ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Clinical Implications ◽  
Future Directions ◽  
Adolescents With Autism ◽  
Memory Flexibility ◽  
The Brain

This chapter reviews strengths and weaknesses in executive function (EF) domains, including inhibition, working memory, flexibility, fluency, and planning, in adolescents (age 13–19) with autism spectrum disorder (ASD). Given the dramatic developmental changes in the brain regions that support EF during the period of adolescence, it is critical to evaluate which EF abilities show a distinct profile during this period. As this chapter will demonstrate, youth with ASD show deficits across all domains of EF, particularly in complex tasks that include arbitrary instructions. We describe the fundamental measures for assessing skills in each domain and discuss limitations and future directions for research, as well as clinical implications of these findings for working with youth with ASD.

scholarly journals Cognitive Performance, Aerobic Fitness, Motor Proficiency, and Brain Function Among Children Newly Diagnosed With Craniopharyngioma

2019 ◽  
Vol 25 (04) ◽  
pp. 413-425 ◽  
Author(s):  
Heather M. Conklin ◽  
Kirsten K. Ness ◽  
Jason M. Ashford ◽  
Matthew A. Scoggins ◽  
Robert J. Ogg ◽  
...  
Keyword(s):  
Working Memory ◽  
Executive Functions ◽  
Aerobic Fitness ◽  
Memory Task ◽  
Peak Oxygen Uptake ◽  
Neural Activation ◽  
Proton Radiation ◽  
Cognitive Changes ◽  
Motor Proficiency ◽  
Network Activation

AbstractObjectives: Craniopharyngioma survivors experience cognitive deficits that negatively impact quality of life. Aerobic fitness is associated with cognitive benefits in typically developing children and physical exercise promotes recovery following brain injury. Accordingly, we investigated cognitive and neural correlates of aerobic fitness in a sample of craniopharyngioma patients. Methods: Patients treated for craniopharyngioma [N=104, 10.0±4.6 years, 48% male] participated in fitness, cognitive and fMRI (n=51) assessments following surgery but before proton radiation therapy. Results: Patients demonstrated impaired aerobic fitness [peak oxygen uptake (PKVO2)=23.9±7.1, 41% impaired (i.e., 1.5 SD&lt;normative mean)], motor proficiency [Bruininks-Oseretsky (BOT2)=38.6±9.0, 28% impaired], and executive functions (e.g., WISC-IV Working Memory Index (WMI)=96.0±15.3, 11% impaired). PKVO2 correlated with better executive functions (e.g., WISC-IV WMI r=.27, p=.02) and academic performance (WJ-III Calculation r=.24, p=.04). BOT2 correlated with better attention (e.g., CPT-II omissions r=.26, p=.04) and executive functions (e.g., WISC-IV WMI r=.32, p=.01). Areas of robust neural activation during an n-back task included superior parietal lobule, dorsolateral prefrontal cortex, and middle and superior frontal gyri (p&lt;.05, corrected). Higher network activation was associated with better working memory task performance and better BOT2 (p&lt;.001). Conclusions: Before adjuvant therapy, children with craniopharyngioma demonstrate significantly reduced aerobic fitness, motor proficiency, and working memory. Better aerobic fitness and motor proficiency are associated with better attention and executive functions, as well as greater activation of a well-established working memory network. These findings may help explain differential risk/resiliency with respect to acute cognitive changes that may portend cognitive late effects. (JINS, 2019, 25, 413–425)

scholarly journals Examining Brain-Cognition Effects of Ginkgo Biloba Extract: Brain Activation in the Left Temporal and Left Prefrontal Cortex in an Object Working Memory Task

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
R. B. Silberstein ◽  
A. Pipingas ◽  
J. Song ◽  
D. A. Camfield ◽  
P. J. Nathan ◽  
...  
Keyword(s):  
Working Memory ◽  
Ginkgo Biloba ◽  
Memory Task ◽  
Random Order ◽  
Ginkgo Biloba Extract ◽  
Task Completion ◽  
Double Blind ◽  
Age Related ◽  
Behavioral Studies ◽  
Electrophysiological Studies

Ginkgo Biloba extract (GBE) is increasingly used to alleviate symptoms of age related cognitive impairment, with preclinical evidence pointing to a pro-cholinergic effect. While a number of behavioral studies have reported improvements to working memory (WM) associated with GBE, electrophysiological studies of GBE have typically been limited to recordings during a resting state. The current study investigated the chronic effects of GBE on steady state visually evoked potential (SSVEP) topography in nineteen healthy middle-aged (50-61 year old) male participants whilst completing an object WM task. A randomized double-blind crossover design was employed in which participants were allocated to receive 14 days GBE and 14 days placebo in random order. For both groups, SSVEP was recorded from 64 scalp electrode sites during the completion of an object WM task both pre- and 14 days post-treatment. GBE was found to improve behavioural performance on the WM task. GBE was also found to increase the SSVEP amplitude at occipital and frontal sites and increase SSVEP latency at left temporal and left frontal sites during the hold component of the WM task. These SSVEP changes associated with GBE may represent more efficient processing during WM task completion.

scholarly journals Acute Ketamine Administration Alters the Brain Responses to Executive Demands in a Verbal Working Memory Task: an fMRI Study

2004 ◽  
Vol 29 (6) ◽  
pp. 1203-1214 ◽  
Author(s):  
R A E Honey ◽  
G D Honey ◽  
C O'Loughlin ◽  
S R Sharar ◽  
D Kumaran ◽  
...  
Keyword(s):  
Working Memory ◽  
Memory Task ◽  
Verbal Working Memory ◽  
Brain Responses ◽  
Fmri Study ◽  
The Brain

scholarly journals The Neural Basis of Shared Preference Learning

2019 ◽  
Author(s):  
Harry Farmer ◽  
Uri Hertz ◽  
Antonia Hamilton
Keyword(s):  
Social Interactions ◽  
Computational Modelling ◽  
Brain Regions ◽  
The Self ◽  
Neural Activation ◽  
Neural Basis ◽  
Daily Lives ◽  
Neural Processes ◽  
Specific Manner ◽  
The Brain

AbstractDuring our daily lives, we often learn about the similarity of the traits and preferences of others to our own and use that information during our social interactions. However, it is unclear how the brain represents similarity between the self and others. One possible mechanism is to track similarity to oneself regardless of the identity of the other (Similarity account); an alternative is to track each confederate in terms of consistency of the similarity to the self, with respect to the choices they have made before (consistency account). Our study combined fMRI and computational modelling of reinforcement learning (RL) to investigate the neural processes that underlie learning about preference similarity. Participants chose which of two pieces of artwork they preferred and saw the choices of one confederate who usually shared their preference and another who usually did not. We modelled neural activation with RL models based on the similarity and consistency accounts. Data showed more brain regions whose activity pattern fits with the consistency account, specifically, areas linked to reward and social cognition. Our findings suggest that impressions of other people can be calculated in a person-specific manner which assumes that each individual behaves consistently with their past choices.

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